Present data suggest that tissue-specific populations of fibroblasts arise during embryonic development. However, it is not known whether the tissue-specific characteristics of each fibroblast-type appear before or after these cells are incorporated into the extracellular matrices of each differentiating tissue. During tissue morphogenesis, the interactions which occur between fibroblasts and epithelial cells are mediated by extracellular matrices synthesized by both cell-types. It therefore is of importance to examine how extracellular macromolecules influence the adhesion, movement, and differentiation of tissue-specific populations of fibroblasts and to elucidate the factors which normally control the biosynthesis and polymerization of extracellular matrices by fibroblasts and epithelial cells. The developing vertebrate eye offers an optimal assortment of differentiating fibroblastic and epithelial cell populations for this study. All cell-types will be grown in vitro. Fibroblast populations from the cornea, limbus, iris, and choroid coat will be studied, as well as the epithelial cells of corneal epithelium, corneal endothelium, and anterior lens epithelium. Immunological techniques will be used to determine the time and location of fibroblast differentiation in vivo during embryonic development. Biochemical assays for mucopolysaccharides, collagens, and elastin will be complemented by ultrastructural techniques in studies of keratan sulfate biosynthesis in corneal fibroblasts, heparan sulfate biosynthesis in differentiating fibroblasts and epithelial cells, and basement membrane formation by epithelial cells. Experiments employing time-lapse cinematography and cell aggregation will determine the role of hyaluronic acid in modifying the mode of movement of cornea fibroblasts during development of the embryonic cornea. BIBLIOGRAPHIC REFERENCES: Conrad, G. W. and G. W. Hart. 1975. Heparan sulfate biosynthesis by embryonic tissues and primary fibroblast populations. Develop. Biol. 44:253-269. Spooner, B. S. and G. W. Conrad. 1975. The role of extracellular materials in cell movement. I. Inhibition of mucopolysaccharide synthesis does not stop ruffling membrane activity or cell movement. J. Cell Biol. 65:286-297.